5-HT2 receptors are partially involved in the relationship between renin release and delta relative power

A strong relationship was previously described between the nocturnal oscillations of plasma renin activity (PRA) and the sleep cycles, with levels of PRA that increase during non rapid eye movement sleep and decrease during rapid eye movement sleep. This study was designed to determine whether ritanserin, a 5-hydroxytryptamine-2 (5-HT2) receptor antagonist known to increase slow wave sleep both in human and in animals and to decrease plasma renin activity response to serotonergic stimulation in the rat, would uncouple this relationship. Eight subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin administered in the morning. They were subjected to 8 hour polysomnography, including spectral analysis of the electroencephalogram and to continuous blood sampling. Blood was sampled from 2300 to 700h every 10 min and plasma renin activity (PRA) was measured by radioimmunoassay of angiotensin 1. The nocturnal profiles were analysed using the pulse detection program ULTRA. Ritanserin produced the expected increase in slow wave sleep (SWS) duration (132 +/- 10 min under ritanserin vs 72 +/- 9 min under placebo; p < 0.001) and a significant increase in delta relative power (69 +/- 2% under ritanserin vs 60 +/- 2% under placebo; p < 0.01). The mean overnight PRA levels had a tendency to decrease under ritanserin (1.66 +/- 0.34 ngAngl/ml per h under ritanserin vs 1.48 +/- 0.31 ngAngl/ml per h under placebo; p = 0.08). Individual PRA oscillations were preserved and remained strongly associated with delta power oscillations. PRA peak levels were similar in both experimental conditions, but the absolute amplitude of the oscillations was decreased under ritanserin (1.50 +/- 0.36 ngAngl/ml per h vs 1.04 +/- 0.14 ngAngl/ml per h; p < 0.05). These results demonstrate that ritanserin, at a dose that augments delta power, only weakly affects renin release, which suggests that 5-HT2 receptors are only partially involved in the processes coupling renin release and SWS and that other mechanisms probably control the sleep-associated variations in PRA.